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3r90

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Revision as of 07:40, 5 August 2016

Crystal structure of Malignant T cell-amplified sequence 1 protein

Structural highlights

3r90 is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	MCTS1, MCT1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MCTS1_HUMAN] Anti-oncogene that play a role in cell cycle regulation; decreases cell doubling time and anchorage-dependent growth; shortens the duration of G1 transit time and G1/S transition. When constituvely expressed, increases CDK4 and CDK6 kinases activity and CCND1/cyclin D1 protein level, as well as G1 cyclin/CDK complex formation. Plays a role as translation enhancer; Recruits the density-regulated protein/DENR and binds to the cap complex of the 5'-terminus of mRNAs, subsequently altering the mRNA translation profile; Up-regulates protein levels of BCL2L2, TFDP1, MRE11A, CCND1 and E2F1, while mRNA levels remains constant. Hyperactivates DNA damage signaling pathway; increased gamma-irradiation-induced phosphorylation of histone H2AX, and induces damage foci formation. Increases the overall number of chromosomal abnormalities such as larger chromosomes formation and multiples chromosomal fusions when overexpressed in gamma-irradiated cells. May play a role in promoting lymphoid tumor development: lymphoid cell lines overexpressing MCTS1 exhibit increased growth rates and display increased protection against apoptosis. May contribute to the pathogenesis and progression of breast cancer via promotion of angiogenesis through the decline of inhibitory THBS1/thrombospondin-1, and inhibition of apoptosis. Involved in the process of proteasome degradation to down-regulate Tumor suppressor p53/TP53 in breast cancer cell; Positively regulates phosphorylation of MAPK1 and MAPK3.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Publication Abstract from PubMed

A strategy of rationally engineering protein surfaces with the aim of obtaining mutants that are distinctly more susceptible to crystallization than the wild-type protein has previously been suggested. The strategy relies on replacing small clusters of two to three surface residues characterized by high conformational entropy with alanines. This surface entropy reduction (or SER) method has proven to be an effective salvage pathway for proteins that are difficult to crystallize. Here, a systematic comparison of the efficacy of using Ala, His, Ser, Thr and Tyr to replace high-entropy residues is reported. A total of 40 mutants were generated and screened using two different procedures. The results reaffirm that alanine is a particularly good choice for a replacement residue and identify tyrosines and threonines as additional candidates that have considerable potential to mediate crystal contacts. The propensity of these mutants to form crystals in alternative screens in which the normal crystallization reservoir solutions were replaced with 1.5 M NaCl was also examined. The results were impressive: more than half of the mutants yielded a larger number of crystals with salt as the reservoir solution. This method greatly increased the variety of conditions that yielded crystals. Taken together, these results suggest a powerful crystallization strategy that combines surface engineering with efficient screening using standard and alternate reservoir solutions.

Protein crystallization by surface entropy reduction: optimization of the SER strategy.,Cooper DR, Boczek T, Grelewska K, Pinkowska M, Sikorska M, Zawadzki M, Derewenda Z Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):636-45. Epub 2007, Apr 21. PMID:17452789^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Prosniak M, Dierov J, Okami K, Tilton B, Jameson B, Sawaya BE, Gartenhaus RB. A novel candidate oncogene, MCT-1, is involved in cell cycle progression. Cancer Res. 1998 Oct 1;58(19):4233-7. PMID:9766643
↑ Dierov J, Prosniak M, Gallia G, Gartenhaus RB. Increased G1 cyclin/cdk activity in cells overexpressing the candidate oncogene, MCT-1. J Cell Biochem. 1999 Sep 15;74(4):544-50. PMID:10440924
↑ Herbert GB, Shi B, Gartenhaus RB. Expression and stabilization of the MCT-1 protein by DNA damaging agents. Oncogene. 2001 Oct 11;20(46):6777-83. PMID:11709712 doi:10.1038/sj.onc.1204881
↑ Shi B, Hsu HL, Evens AM, Gordon LI, Gartenhaus RB. Expression of the candidate MCT-1 oncogene in B- and T-cell lymphoid malignancies. Blood. 2003 Jul 1;102(1):297-302. Epub 2003 Mar 13. PMID:12637315 doi:10.1182/blood-2002-11-3486
↑ Levenson AS, Thurn KE, Simons LA, Veliceasa D, Jarrett J, Osipo C, Jordan VC, Volpert OV, Satcher RL Jr, Gartenhaus RB. MCT-1 oncogene contributes to increased in vivo tumorigenicity of MCF7 cells by promotion of angiogenesis and inhibition of apoptosis. Cancer Res. 2005 Dec 1;65(23):10651-6. PMID:16322206 doi:10.1158/0008-5472.CAN-05-0845
↑ Hsu HL, Shi B, Gartenhaus RB. The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells. Oncogene. 2005 Jul 21;24(31):4956-64. PMID:15897892 doi:10.1038/sj.onc.1208680
↑ Reinert LS, Shi B, Nandi S, Mazan-Mamczarz K, Vitolo M, Bachman KE, He H, Gartenhaus RB. MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles. Cancer Res. 2006 Sep 15;66(18):8994-9001. PMID:16982740 doi:66/18/8994
↑ Hsu HL, Choy CO, Kasiappan R, Shih HJ, Sawyer JR, Shu CL, Chu KL, Chen YR, Hsu HF, Gartenhaus RB. MCT-1 oncogene downregulates p53 and destabilizes genome structure in the response to DNA double-strand damage. DNA Repair (Amst). 2007 Sep 1;6(9):1319-32. Epub 2007 Apr 6. PMID:17416211 doi:10.1016/j.dnarep.2007.02.028
↑ Nandi S, Reinert LS, Hachem A, Mazan-Mamczarz K, Hagner P, He H, Gartenhaus RB. Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage. Oncogene. 2007 Apr 5;26(16):2283-9. Epub 2006 Oct 2. PMID:17016429 doi:10.1038/sj.onc.1210030
↑ Cooper DR, Boczek T, Grelewska K, Pinkowska M, Sikorska M, Zawadzki M, Derewenda Z. Protein crystallization by surface entropy reduction: optimization of the SER strategy. Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):636-45. Epub 2007, Apr 21. PMID:17452789 doi:10.1107/S0907444907010931

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3r90"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Malignant T cell-amplified sequence 1 protein==
 <StructureSection load='3r90' size='340' side='right' caption='[[3r90]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3r90]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R90 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R90 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3r90]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R90 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R90 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCTS1, MCT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCTS1, MCT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r90 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r90 RCSB], [http://www.ebi.ac.uk/pdbsum/3r90 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r90 OCA], [http://pdbe.org/3r90 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3r90 RCSB], [http://www.ebi.ac.uk/pdbsum/3r90 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3r90 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3r90" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Arrowsmith, C H]]
 [[Category: Bountra, C]]

3r90

From Proteopedia

Revision as of 07:40, 5 August 2016

Crystal structure of Malignant T cell-amplified sequence 1 protein

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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